We intend to achieve a better understanding of the pathogenesis and treatment of human hyperlipidemia through studies of genetic and environmental factors which affect lipoprotein metabolism. We have defined a complex array of VLDL-apo E isoproteins and are beginning to understand the origin and function of these isoproteins. These studies are providing insight into the inheritance of type III hyperlipoproteinemia and appear to provide the basis for identifying a common atherosclerosis gene in the population. We had also described human apo A-I isoproteins and demonstrated that apo A-I synthesized is converted after secretion to the major isoprotein forms found in plasma. Through these studies we hope to reveal the underlying defect in Tangier Disease.